DEAR PHARMACIST

Excitement builds for a new sleep drug

Published: Tuesday, April 30, 2013 at 6:01 a.m.

Last Modified: Monday, April 29, 2013 at 4:16 p.m.

Q: I can't sleep well and have taken Ambien for years. What else do you recommend?

— F.T., Bradenton

A: If you can't sleep on Ambien, I'd try something different. Another novel sleep drug is coming to the market called "Suvorexant" and so far, I like it. The Food and Drug Administration (FDA) is evaluating it right now.

Merck & Co is manufacturing the new drug, which supposedly does not induce memory loss, daytime fatigue or attention difficulties, all common side effects with benzodiazepines and Z drugs, which dominate the multi-billion dollar insomnia market. You know them by names like Ambien, Lunest, Sonata, Xanax, Valium and Halcion.

The drugs increase GABA levels, a neurotransmitter that induces sleep. Tickle those GABA receptors, and you will fall asleep, and likely have cognitive problems, full-body muscle relaxation, daytime fatigue and bizarre hypnotic events. Anything's possible. Suvorexant doesn't affect GABA at all, it reduces a hormone called orexin (a.k.a. hypocretin). This drug doesn't induce sleep, rather it turns off the switch that keeps you awake.

Interestingly, elevated orexin are common in those prone to panic attacks (Nature Medicine, 2010), but that is not Suvorexant's focus, it's marketed as a prescription sleep aid and will do very well. There are well-designed unbiased clinical trials to show orexin blockers improve sleep (and reduce panic). If you have sleep deprivation, it increases risk of depression, heart disease and infection, so sleep any way you can.

Orexins keep you awake. If orexin levels suddenly drop, so do you, meaning you go to sleep. People with narcolepsy have swinging orexin levels. Contrarily, if orexin is high, you might feel panicky, anxious, wired or have insomnia. That's where Suvorexant works, it reduces orexin, and remember orexin keeps you awake. It's categorized as a "dual orexin receptor antagonist" or a "DORA blocker" for short. Dual because it blocks both OX1 and OX2 receptor sites.

How do you feel if you wake at 4 a.m. on your sleep medication? Researchers compared conventional GABA blockers to DORA blockers to find out. Monkeys given popular GABA blockers were much foggier, confused and slower to respond as compared to monkeys given a DORA blocker. We're not monkeys, though the point is made.

Is Suvorexant the next best amazing sleep drug? Time will tell. So far, headache is the most commonly reported side effect. Always use the lowest effective dose and for short-terms. Never combine sleep drugs with sedatives or alcohol. Clean your bedroom, turn off lights and implement healthier sleep hygiene practices; go to my website to read about natural remedies if those interest you. One theoretical concern is narcolepsy. If you reduce orexin levels, you will go to sleep. That's the point of the drug. Fortunately, late-stage clinical trials have not reported this side effect. More adverse reactions may trickle after the medication is launched. Sleep aids are for short-term use, they are not a forever thing.

This column is not intended to treat, cure or diagnose you. To submit a question visit www.DearPharmacist.com.

<p><b>Q:</b> I can't sleep well and have taken Ambien for years. What else do you recommend?</p><p><i>— F.T., Bradenton</i></p><p><b>A:</b> If you can't sleep on Ambien, I'd try something different. Another novel sleep drug is coming to the market called "Suvorexant" and so far, I like it. The Food and Drug Administration (FDA) is evaluating it right now.</p><p>Merck & Co is manufacturing the new drug, which supposedly does not induce memory loss, daytime fatigue or attention difficulties, all common side effects with benzodiazepines and Z drugs, which dominate the multi-billion dollar insomnia market. You know them by names like Ambien, Lunest, Sonata, Xanax, Valium and Halcion.</p><p>The drugs increase GABA levels, a neurotransmitter that induces sleep. Tickle those GABA receptors, and you will fall asleep, and likely have cognitive problems, full-body muscle relaxation, daytime fatigue and bizarre hypnotic events. Anything's possible. Suvorexant doesn't affect GABA at all, it reduces a hormone called orexin (a.k.a. hypocretin). This drug doesn't induce sleep, rather it turns off the switch that keeps you awake. </p><p>Interestingly, elevated orexin are common in those prone to panic attacks (Nature Medicine, 2010), but that is not Suvorexant's focus, it's marketed as a prescription sleep aid and will do very well. There are well-designed unbiased clinical trials to show orexin blockers improve sleep (and reduce panic). If you have sleep deprivation, it increases risk of depression, heart disease and infection, so sleep any way you can. </p><p>Orexins keep you awake. If orexin levels suddenly drop, so do you, meaning you go to sleep. People with narcolepsy have swinging orexin levels. Contrarily, if orexin is high, you might feel panicky, anxious, wired or have insomnia. That's where Suvorexant works, it reduces orexin, and remember orexin keeps you awake. It's categorized as a "dual orexin receptor antagonist" or a "DORA blocker" for short. Dual because it blocks both OX1 and OX2 receptor sites. </p><p>How do you feel if you wake at 4 a.m. on your sleep medication? Researchers compared conventional GABA blockers to DORA blockers to find out. Monkeys given popular GABA blockers were much foggier, confused and slower to respond as compared to monkeys given a DORA blocker. We're not monkeys, though the point is made. </p><p>Is Suvorexant the next best amazing sleep drug? Time will tell. So far, headache is the most commonly reported side effect. Always use the lowest effective dose and for short-terms. Never combine sleep drugs with sedatives or alcohol. Clean your bedroom, turn off lights and implement healthier sleep hygiene practices; go to my website to read about natural remedies if those interest you. One theoretical concern is narcolepsy. If you reduce orexin levels, you will go to sleep. That's the point of the drug. Fortunately, late-stage clinical trials have not reported this side effect. More adverse reactions may trickle after the medication is launched. Sleep aids are for short-term use, they are not a forever thing.</p><p><i>This column is not intended to treat, cure or diagnose you. To submit a question visit www.DearPharmacist.com.</i></p>